In this project, we seek to l) clarify and expand the nosology of the hereditary movement disorders; 2) contribute to the understanding of the underlying biochemical basis; 3) determine the most effective treatment for each disorder; and 4) suggest guidelines for counseling individuals at risk. General syndromes under study include the dystonias, tic disorders, blepharospasm, and myoclonus. Approaches include standard epidemiologic and clinical genetic studies together with collaborative efforts in evaluating the role of neurotransmitters such as dopamine, their precursors, and metabolites, and their necessary cofactors. Collaborative studies are underway with personnel in LCS, DCBR, MIMH to explain our earlier observations of altered dopamine beta hydroxylase and norepinephrine levels in blood and biopterin in CSF in a genetic subset of dystonia patients. Members of selected families are being brought to the Clinical Center, NIH, for trial of several new pharmacological agents. Biopterin administered intravenously has led to acute benefit in one form of generalized dystonia.